1. Field of the Invention
The present invention relates to methods for the treatment of chronic obstructive pulmonary disease (COPD) and asthma. In particular the invention relates to the treatment of COPD and asthma by administering type V Collagen (colV) or tolerogenic fragments thereof.
2. Description of the Related Art
Chronic obstructive pulmonary disease (COPD) is a group of diseases of the lungs in which the airways become narrowed. This leads to a limitation of the flow of air to and from the lungs causing shortness of breath. In contrast to asthma, the limitation of airflow is poorly reversible and usually gets progressively worse over time. COPD is also known as chronic obstructive lung disease (COLD), chronic obstructive airway disease (COAD), chronic airflow limitation (CAL) and chronic obstructive respiratory disease. The term “COPD” includes two main conditions—emphysema and chronic obstructive bronchitis.
In emphysema, the walls between many of the air sacs are damaged, causing them to lose their shape and become floppy. This damage also can destroy the walls of the air sacs, leading to fewer and larger air sacs instead of many tiny ones.
In chronic obstructive bronchitis, the lining of the airways is constantly irritated and inflamed. This causes the lining to thicken. Lots of thick mucus forms in the airways, making it hard to breathe.
Most people who have COPD have both emphysema and chronic obstructive bronchitis. Thus, the general term “COPD” is more accurate.
Chronic bronchitis and emphysema are most commonly caused by smoking; approximately 90% of patients with COPD are or were smokers. Although approximately 50% of smokers develop chronic bronchitis, only 15% of smokers develop disabling airflow obstruction. Certain other mammals, particularly horses, suffer from COPD as well.
The airflow obstruction associated with COPD is progressive, may be accompanied by airway hyperreactivity, and may be partially reversible. Non-specific airway hyper-responsiveness may also play a role in the development of COPD and may be predictive of an accelerated rate of decline in lung function in smokers.
COPD is a significant cause of death and disability. It is currently the fourth leading cause of death in the United States and Europe. Treatment guidelines advocate early detection and implementation of smoking cessation programs to help reduce morbidity and mortality due to the disease. However, early detection and diagnosis has been difficult for a number of reasons.
COPD takes years to develop and smokers often deny any ill effects from smoking, attributing the early warning signs of increased breathlessness as a sign of age. Similarly, acute episodes of bronchitis often are not recognized by the general practitioner as early signs of COPD. Many patients exhibit features of more than one disease (e.g. chronic bronchitis or asthmatic bronchitis) making precise diagnosis a challenge, particularly in early disease. Also, many patients do not seek medical help until they are experiencing more severe symptoms associated with reduced lung function, such as dyspnea, persistent cough, and sputum production. As a consequence, the vast majority of patients are not diagnosed or treated until they are in a more advanced stage of disease.
Asthma is a heterogeneous disorder of the airways that afflicts millions of people. Airway inflammation, hyperresponsiveness, and obstruction characterize the condition. The disease often causes spasms of the bronchial smooth muscle system, and affects both the upper and lower respiratory tracts. There are several forms of asthma, characterized by varying degrees of severity. Mild asthma, for example, is defined as brief episodes of wheezing, with or without dyspnea or cough. Moderately severe asthma is defined as wheezing and dyspnea, and can be with or without cough and expectoration, but generally interferes with daily activities and/or sleeping. Severe asthma is characterized by incapacitation due to dyspnea, and the afflicted patient typically is unable to eat or sleep normally, is very anxious, and is often exhausted. A condition known as status asthmaticus is the most severe form of asthma, and generally requires intensive hospital care, and may even prove fatal. The disease may occur as a result of both allergic and nonallergic mechanisms.
While there are several treatments available for relieving the symptoms and discomfort associated with asthma, there are no cures. Moreover, the current treatments often cause side effects that exacerbate the discomfort and precipitate other debilitating conditions. Mild asthma generally is treated with beta-adrenergic drugs, as well as antihistamines, especially in the case of children, to prevent or abort sporadic episodes. Moderately severe and severe asthma are generally treated with adrenergic agents and bronchodilators, as well as corticosteroids. Other actions caused by antiasthmatic agents which limit their widespread use include headache, fatigue, dry mouth, nervousness, and in some cases addiction and substance abuse. Recent advances in the understanding of the pathogenesis and treatment of asthma is discussed more fully in Am J Respir Crit. Care Med. 2008 May 15; 177(10):1068-73.
Because asthma is so prevalent in both children and adults, there is an ongoing need for agents that can treat the disease, or at least relieve the symptoms that accompany the disease, without causing undesirable side effects. Likewise, there is an ongoing need for compositions and methods for treating COPD. The present invention provides compositions and methods for the treatment of COPD and asthma and other advantages as described in the detailed description.